ABSTRACT Through the pilot component of the Autonomic RDCRC, the five institutions comprising this Consortium will collaborate in the choice and conduct of pilot projects, designed to take advantage of new clinical research opportunities in Rare Autonomic Disorders. As the investigators develop new insights into pathophysiology or novel potential interventions that might impact targeted autonomic diseases, the Pilot Projects Committee can assess the promise and novelty of proposed interventions. It is noteworthy that concepts for pilots can emanate not only from consortium investigators but can be submitted from other medical scientists in the field even if from a non-consortium institution, or from individuals in the Coalition of Patient Advocacy Groups (CPAG). Promising concepts will be considered by the Pilot Projects Program Committee. Upon discussion by the Committee, the consortium PIs may then propose to conduct a pilot study. The focus of a pilot study may be the development of a new assay or clinical instrument, or it could be an assessment of the therapeutic potential of a new medication. The primary criteria used to select pilot studies will be their potential implications for diagnosis and treatment of autonomic disorders. As pilot results are successful they can be incorporated into existing projects or develop into new projects. We include three pilot studies. Pilot Study 1 examines blood and imaging biomarkers that can aid in early diagnosis of multiple system atrophy, an area of obvious importance to several of the projects proposed in the Consortium. Pilot Study 2 proposes a novel approach using 3,4-diaminopyridine (3,4-DAP) to facilitate autonomic neurotransmission and harness residual sympathetic tone to treat orthostatic hypotension in autonomic failure patients. Pilot Study 3 takes advantage of the unique patient population with postural tachycardia syndrome (POTS), characterized with high sympathetic tone, very low parasympathetic cardiac modulation, and elevated indices of inflammation. Vagus nerve stimulation will be used to test the cholinergic anti-inflammatory reflex.